Ever since the dawn of the clinical trial, critics have questioned whether the people being studied represent the actual patients who will take a drug in the real world. In other words, how applicable are the results from a carefully chosen cohort to the entire spectrum of patients with comorbidities?

That question takes on new urgency in an era of expensive immunotherapy treatments, especially among the public agencies that make financial decisions about what to reimburse: These officials seek solid evidence a therapy is going to be effective for most of the patients who will take it.

For example, Danish clinical scientist Marco Donia, MD, PhD, who studies melanoma at Denmark’s National Center for Cancer Immune Therapy in Copenhagen, was frustrated that recent randomized phase 3 trials for several immune checkpoint inhibitors to treat metastatic melanoma left out more than half of patients who show up at the country’s health centers.1 “We found that there’s a real gap between the patient population enrolled in clinical trials and the real world,” he said to Cancer Therapy Advisor, noting that such trials didn’t include patients whose disease had progressed or those who suffered from active brain metastases. “Without more data, we can’t evaluate what we’re going to get for the money,” said Dr Donia, who heads his organization’s subcommittee that determines whether state hospitals should be reimbursed for prescribing immunotherapies. “At more than $100,000 a year for the list price, they’re expensive and create a huge burden on the health care system.”

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To make up for the lack of evidence, Dr Donia and his team crunched the numbers to tally how many patients had been diagnosed with metastatic melanoma in the state health care system. In research published in July 2019 in the journal Oncotarget, they found the proof they needed to justify paying for immunotherapy drugs: Patients who were treated in 2016 — when first-line anti–PD-1 and MEK inhibitors became available — had better survival outcomes than those treated in 2014 and 2012 with other classes of drugs.The authors concluded that the new immunotherapies were effective for all patient subgroups, despite the fact that the clinical trials only produced data for a narrow group that met strict criteria.


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That conclusion inspired Dr Donia to encourage his peers to ask for such “real-world data” to supplement clinical trial research when making critical payment decisions. Dr Donia’s call to use such real-world data has a long history in a field like oncology, in which actual patients aren’t well represented in randomized controlled clinical trials — a stark reality that in 2017 prompted the American Society of Clinical Oncology and Friends of Cancer Research to jointly issue a statement calling to broaden eligibility criteria to make clinical trials more relevant.3

It’s not only the price of immunotherapy drugs that is motivating calls for more data. The fact that these drugs might work differently across various population groups means that investigators need as many data points as possible, according to Bassel Nazha, MD, MPH, a hematology and medical oncology fellow at the Emory University School of Medicine in Atlanta, Georgia. “Patients who are included in clinical trials are highly selected. They tend to be Caucasian and male. The patients who are less likely to be included are elderly, are from a racial minority, or have kidney or liver disease,” said Dr Nazha. In other words, the people in trial often are not representative of the people he sees in his clinic.